Nitric oxide is a mediator of hypoxic coronary vasodilatation. Relation to adenosine and cyclooxygenase-derived metabolites.
Nitric oxide is a mediator of hypoxic coronary vasodilatation. Relation to adenosine and cyclooxygenase-derived metabolites.
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一氧化氮是缺氧冠状血管舒张的介质。
DOI：
10.1161/01.res.71.4.992
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发表时间：
1992
影响因子：
20.1
通讯作者：
Levi,R
中科院分区：
文献类型：
--
作者：
Park,KH;Rubin,LE;Gross,SS;Levi,R
缺氧是一个强有力的冠状动脉舒张信号；其机制仍有争议。我们已经评估了一氧化氮（NO）在离体豚鼠心脏恒压灌注缺氧冠状动脉血管扩张（HCVD）中的可能作用。HCVD由100% N2暴露1分钟引起；冠状动脉血流在缺氧1分钟内翻倍（早期），在复氧后40秒内恢复到基线（晚期）。HCVD早期与cGMP溢出快速增加约8倍相关，cGMP溢出是NO释放的一个指示。特异性NO合成酶抑制剂N - omega-甲基- l-精氨酸（NMA, 0.1-1 mM）可拮抗HCVD，并增加cGMP溢出（最大抑制，约65%）；过量精氨酸（1.2 mM）阻止了这两种效果。晚期HCVD与腺苷溢出增加有关，并被腺苷受体拮抗剂BW A1433减弱（1微米；最大抑制作用约为45%）。吲哚美辛（10微米）对自发跳动的心脏的HCVD抑制作用约为35%，但对心律加快的心脏没有作用。NMA和BW A1433联合使用比单独使用更有效（最大抑制率约为72%）。然而，无论使用何种浓度，NMA、BW A1433和吲哚美辛的抗HCVD作用之间没有协同作用，而且无论是单独使用还是联合使用，HCVD也不能完全被拮抗剂抑制。我们的研究结果表明，NO是HCVD早期阶段的重要介质，而其他机制和/或因素，包括腺苷和血管舒张性前列腺素，有助于后期阶段。
Hypoxia is a potent coronary-vasodilating signal; its mechanisms are still controversial. We have assessed the possible role of nitric oxide (NO) in hypoxic coronary vasodilatation (HCVD) in isolated guinea pig hearts perfused at constant pressure. HCVD was elicited by a 1-minute 100% N2 exposure; coronary flow doubled within 1 minute of hypoxia (early phase) and returned to baseline within 40 seconds after reoxygenation (late phase). The early phase of HCVD was associated with a rapid approximately eightfold increase in cGMP overflow, an indication of NO release. The specific NO synthase inhibitor N omega-methyl-L-arginine (NMA, 0.1-1 mM) antagonized HCVD and the associated increase in cGMP spillover (maximum inhibition, approximately 65%); excess arginine (1.2 mM) prevented both effects. The late phase of HCVD was associated with an increase in adenosine overflow and was attenuated by the adenosine receptor antagonist BW A1433 (1 microM; maximum inhibition, approximately 45%). Indomethacin (10 microM) inhibited HCVD in spontaneously beating hearts by approximately 35% but had no effect in hearts paced at faster rates. NMA and BW A1433 were more effective in combination than alone (maximum inhibition, approximately 72%). However, irrespective of the concentrations used, there was no synergism among the anti-HCVD effects of NMA, BW A1433, and indomethacin, nor was HCVD completely inhibited by the antagonists, whether alone or in combination. Our findings indicate that NO is an important mediator of the early phase of HCVD, whereas additional mechanisms and/or factors, including adenosine and vasodilatatory prostaglandins, contribute to the late phase.